WO2007034196A2 - Imaging agents comprising silicon - Google Patents
Imaging agents comprising silicon Download PDFInfo
- Publication number
- WO2007034196A2 WO2007034196A2 PCT/GB2006/003522 GB2006003522W WO2007034196A2 WO 2007034196 A2 WO2007034196 A2 WO 2007034196A2 GB 2006003522 W GB2006003522 W GB 2006003522W WO 2007034196 A2 WO2007034196 A2 WO 2007034196A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- silicon
- imaging
- agent
- previous
- porous silicon
- Prior art date
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- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 190
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- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
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- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
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- A61K51/1241—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins
- A61K51/1244—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins microparticles or nanoparticles, e.g. polymeric nanoparticles
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- A61B6/00—Apparatus for radiation diagnosis, e.g. combined with radiation therapy equipment
- A61B6/50—Clinical applications
- A61B6/506—Clinical applications involving diagnosis of nerves
Definitions
- Imaging agents may also be used to accurately position a body, or part of a body, including an organ or tissue, in the correct orientation or field of view for imaging or therapeutic treatment.
- imaging modalities may be used in assessing the treatment of lesions by, for example, chemotherapy, surgery and radiation therapy.
- chemotherapy drugs are introduced into the patient's body to destroy the lesion.
- a variety of imaging modalities may be implemented to follow the progress of the treatment or condition by comparing a series of images of a particular treatment site over time. Positional information obtained from the images may be used before and/or during the performance of a medical procedure at the site of the lesion.
- one or more imaging modalities may be useful in imaging the site of lesion removal, and/or the whole body, to monitor the condition of the site and the patient. Imaging of the removed sample can also be used to ensure the lesion of interest has been successfully removed and is contained within the surgical specimen.
- tissue markers immediately after or during the biopsy procedure.
- the marker e.g., a radiopaque material, can be used to help locate the biopsy site in case malignancy is determined, thereby enabling return to the same site and optionally a subsequent treatment such as surgical excision, even if the mammographic findings associated with the original lesions were removed completely.
- the imaging agent may be in the form of a positioning aid, for example, to provide an image of surgical tools that have inadvertently been left inside a patient or for surgical implants or other objects which are purposely inserted into a patient.
- a positioning aid for example, to provide an image of surgical tools that have inadvertently been left inside a patient or for surgical implants or other objects which are purposely inserted into a patient.
- Suitable examples include coronary or oesophageal stents, intercostal tubes, endotracheal tubes, nasogastric tubes, intravenous canulas and the like, or as part of an orthopaedic implant.
- the inclusion of radiopaque or ultrasound visible markings will confirm that the product has been correctly positioned during insertion.
- Fusing into a conjoint study also referred to as hybrid imaging, utilises software and/or hardware whereby two or more imaging data sets are merged into a standard anatomical volume to provide improved localisation and/or enhanced information based on the separate finding within each imaging modality.
- silicon refers to solid elemental silicon.
- silicon-containing chemical compounds such as silica, silicates or silicones, although it may be used in combination with these materials.
- the silicon may be about 98 to 99.999999% pure, preferably 99 to 99.999% pure and even more preferably 99.9 to 99.999% pure.
- the physical forms of silicon which are suitable for use in the present invention may be chosen from or comprise amorphous silicon, single crystal silicon and polycrystalline silicon (including nanocrystalline silicon, the grain size of which is typically taken to be 1 to 100nm), bulk crystalline silicon and including combinations thereof.
- porous silicon which may be referred to as "pSi".
- the silicon may be surface porosified, for example, using a stain etch method, a gas etch method or more substantially porosified, for example, using an anodisation technique.
- Preferred forms of porous silicon for use in the present invention are mesoporous, microporous or macroporous silicon.
- Microporous silicon contains pores possessing a diameter less than 2nm; mesoporous silicon contains pores having a diameter in the range of 2 to 50nm; and macroporous silicon contains pores having a diameter greater than 50nm.
- Suitable metals include one or more of the following: cadmium, cesium, cobalt, copper, gallium, lead, manganese, molybdenum, niobium, rubidium, ruthenium, scandium, technetium, titanium, gold, tantalum, iridium, platinum, tungsten, rhodium, palladium, strontium, samarium, thallium, holmium, scandium, zirconium, yttrium, silver, iron, gadolinium, chromium, zinc, barium, magnesium, calcium, including all stable and unstable isotopes of these atoms.
- Other suitable materials include stainless steel.
- Metallic ions such as, for example, iron, manganese and gadolinium may be used in combination with the silicon for use in combination with MRI imaging systems.
- Preferred gases may comprise, for example, one or more of the following: nitrogen; oxygen; carbon dioxide; hydrogen; nitrous oxide; a noble or inert gas such as helium, neon, argon, radon, xenon or krypton; a radioactive gas; a hyperpolarized noble gas such as hyperpolarized argon; a low molecular weight hydrocarbon; a cycloalkane; an alkene; an alkyne; an ether; a ketone; an ester; sulfur-based gases; halogenated gases, preferably fluorinated gases, including, for example, partially fluorinated gases or completely fluorinated gases such as sulphur hexafluoride, fluorohydrocarbons, perfluorocarbons, fluorocarbon gases, other fluorinated halogenated organic compounds in the gas phase, and mixtures thereof.
- a noble or inert gas such as helium, neon, argon, radon, xenon or
- Preferred formulations may also comprise, for example, one or more of the emulsifying agents and/or emulsion stabilizers contained in the lists below.
- Suitable suspending agents include acacia, agar, alginic acid, bentonite, calcium stearate, carbomers, carboxymethylcellulose calcium, carboxymethylcellulose sodium, carrageenan, cellulose (microcrystalline), cellulose (powdered), ceratonia, colloidal silicon dioxide, dextrin, gelatin, guar gum, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl cellulose, hypromellose, kaolin, magnesium aluminum silicate, maltitol solution, medium-chain triglycerides, methylcellulose, polycarbophil, polyethylene glycol, polyoxyethylene sorbitan fatty acid esters, potassium alginate, povidone, propylene glycol alginate, sesame oil, sodium alginate, sodium starch glycolate, sorbitan esters (sorbitan fatty acid esters), sucrose, tragacanth, xanthan gum.
- Suitable coatings include acetyltributyl citrate, acetyltriethyl citrate, aliphatic polyesters, calcium carbonate, carbomers, carboxymethylcellulose sodium, cellulose acetate, cellulose acetate phthalate, cetyl alcohol, chitosan, ethylcellulose, fructose, gelatin, glycerin, glyceryl behenate, glyceryl palmitostearate, guar gum, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl cellulose, hypromellose, hypromellose acetate succinate, hypromellose phthalate, isomalt, latex particles, maltitol, maltodextrin, methylcellulose, poloxamer, polydextrose, polyethylene glycol, polymethacrylates, polyvinyl acetate phthalate, polyvinyl alcohol, potassium chloride, povidone, shellac, shella
- the manufacturing process for the imaging agent may employ the use of excipients, for example, one or more of the following: lubricants (canola oil, codliver oil, hydroxyethyl cellulose, lauric acid, leucine, mineral oil, octyldodecanol, poloxamers, polyvinyl alcohol, sodium hyaluronate, talc), air displacement agents (carbon dioxide, nitrogen), freeze-drying agents and cryoprotectants (albumin, lactose (anhydrous), mannitol, sodium bicarbonate, trehalose), sterilisation/disinfectant/antiseptic/antibacterial/antifungal/antivirals agents, and/or polishing agents (e.g. yellow wax).
- lubricants canola oil, codliver oil, hydroxyethyl cellulose, lauric acid, leucine, mineral oil, octyldodecanol, poloxamers, polyvinyl alcohol, sodium hy
- particulate silicon which may or may not be porous, may be consolidated to form a multiplicity of bonded silicon particles typically under the influence of pressure.
- the pressure may, for example be applied uniaxially or isostatically. Typical uniaxial pressures may be in the range of 10MPa to 5000MPa and the isostatic pressure may be in the range of 10MPa to 5000MPa.
- the porous unitary body may alternatively be formed by porosifying a pre-shaped unit of bulk silicon, such as a rod or tablet.
- the bulk unit may be porosified by anodisation such that one or more of the bulk units are linked as the anode in an electrolytic cell with the cathode formed by an encompassing inert (for example platinum) mesh in the form of a cylinder or other appropriate shape.
- the bulk unit may be porosified by stain etch such that one or more bulk units are immersed in appropriate HF etching solutions for a sufficient period of time, and where appropriate with agitation and/or circulation of the etchant solution to achieve the desired levels of porosity.
- the imaging agent may be combined with chemical moieties which enable preferential binding to particular cells, cell types, tissues, organs or systems.
- moieties may include ligands, peptides, antibodies, antibody fragments, recombinant proteins and other molecules familiar to those skilled in the art.
- the imaging agent may, optionally, be combined with further chemical moieties to render it more distinguishable from normal anatomy under one or more imaging modalities.
- the carboxymethylcellulose sodium salt (NaCMC) was made up into a 0.5% w/v formulation by weighing out 0.1g of the powder and mixing it with 2OmIs of sterile water for injection. 10ml of the NaCMC solution was added to 15g of the 30 ⁇ m stain- etched poly-Si powder and mixed using a spatula and a vortex mechanical mixer until a homogeneous 1.5g pSi/ml NaCMC suspension was achieved. In some of the experiments, the 1.5g pSi/ml NaCMC suspension proved quite difficult to inject. The pSi/NaCMC suspension and the remaining NaCMC were then transferred to glass vials sealed with an air-tight rubber injection membrane and metal seal to allow storage for later use.
- the right SMLN was identified and the overlying skin was shaved devoid of hair.
- a stab incision was made through the skin and into the SMLN.
- a porous silicon pellet of 5. mm diameter, height 1.35mm, volume 0.026cm 3 , weight 0.047g and density 1.773g/cm 3 was inserted into the middle of the lymphoid tissue, and the incision was filled with ultrasound gel to displace any trapped air. The incision was sutured closed.
- the pSi tattoo may be loaded with antibiotic to minimize the risks of infection. Loading may utilize the techniques described in WO 05042023 the contents of which are hereby incorporated by reference in their entirety.
- Imaging was undertaken at 10MHz, with focus set to 1.3-2cm. Water soluble ultrasound transmission gel, was used to acoustically couple the transducer to the tissue samples. During image acquisition the ultrasound probe was held stationary with respect to the tissue samples and the needle by clamping it in a retort stand. Images were captured immediately prior to the injection (“pre-injection” image), and immediately following the injection (“post-injection image”). All imaging parameters were held constant during acquisition.
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
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AU2006293667A AU2006293667A1 (en) | 2005-09-22 | 2006-09-22 | Imaging agents comprising silicon |
US11/992,292 US20090297441A1 (en) | 2005-09-22 | 2006-09-22 | Imaging Agents |
JP2008531782A JP2009508924A (en) | 2005-09-22 | 2006-09-22 | Contrast agent containing silicon |
CA002622845A CA2622845A1 (en) | 2005-09-22 | 2006-09-22 | Imaging agents comprising silicon |
EP06779521A EP1993614A2 (en) | 2005-09-22 | 2006-09-22 | Imaging agents comprising silicon |
Applications Claiming Priority (2)
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GBGB0519391.7A GB0519391D0 (en) | 2005-09-22 | 2005-09-22 | Imaging agents |
GB0519391.7 | 2005-09-22 |
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WO2007034196A2 true WO2007034196A2 (en) | 2007-03-29 |
WO2007034196A3 WO2007034196A3 (en) | 2007-11-15 |
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PCT/GB2006/003522 WO2007034196A2 (en) | 2005-09-22 | 2006-09-22 | Imaging agents comprising silicon |
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US (1) | US20090297441A1 (en) |
EP (1) | EP1993614A2 (en) |
JP (1) | JP2009508924A (en) |
KR (1) | KR20080067333A (en) |
AU (1) | AU2006293667A1 (en) |
CA (1) | CA2622845A1 (en) |
GB (1) | GB0519391D0 (en) |
WO (1) | WO2007034196A2 (en) |
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Also Published As
Publication number | Publication date |
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EP1993614A2 (en) | 2008-11-26 |
KR20080067333A (en) | 2008-07-18 |
US20090297441A1 (en) | 2009-12-03 |
WO2007034196A3 (en) | 2007-11-15 |
CA2622845A1 (en) | 2007-03-29 |
AU2006293667A1 (en) | 2007-03-29 |
GB0519391D0 (en) | 2005-11-02 |
JP2009508924A (en) | 2009-03-05 |
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